This report describes peroxisomal acyl-CoA oxidase deficiency, which exhibits autosomal recessive inheritance. The gene implicated in this disease is ACOX1, which encodes peroxisomal acyl-CoA oxidase. This enzyme catalyzes the first and rate-limiting enzyme in the peroxisomal fatty acid beta-oxidation pathway. The highest-scoring ortholog in Drosophila is also designated ACOX1; loss-of-function mutations, a gain-of-function allele analogous to human N237S, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\ACOX1.
Multiple UAS constructs of the human Hsap\ACOX1 have been introduced into flies, including wild-type and the N237S variant implicated in Mitchell syndrome (see FBhh0001229).
Animals homozygous for loss-of-function alleles of Dmel\ACOX1 typically die during the pupal stage; adult escapers exhibit progressive locomotor impairment and progressive vision defects leading to vision loss; TEM analysis of peripheral neurons in the wing showed decreased numbers of axons and wrapping glia. A small number of physical and genetic interactions of Dmel\ACOX1 have been described; see below and in the ACOX1 gene report.
This model system has been used to assess the therapeutic effects of a pharmaceutical currently used to treat hyperlipidemia. Both loss and gain of ACOX1 lead to glial and neuronal loss, but by different mechanisms, thus requiring different treatments. (See Mitchell syndrome, FBhh0001229.
[updated Jul. 2020 by FlyBase; FBrf0222196]
[PEROXISOMAL ACYL-CoA OXIDASE DEFICIENCY](https://omim.org/entry/264470)
[ACYL-CoA OXIDASE 1, PALMITOYL; ACOX1](https://omim.org/entry/609751)
The initial report of this disease described 2 patients with neonatal hypotonia, seizures, apneic spells, delayed psychomotor development, and neurologic regression after age 2 years (Poll-The et al., 1988; pubmed:2894756). [from MIM:264470; 2020.07.27]
Peroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures; they may have unusual facial features. Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with peroxisomal acyl-CoA oxidase deficiency do not survive past early childhood. [Genetics Home Reference, Peroxisomal acyl-CoA oxidase deficiency; 2020.07.27]
Peroxisomal acyl-CoA oxidase deficiency is caused by homozygous mutation in the gene encoding peroxisomal straight-chain acyl-CoA oxidase (ACOX1). [from MIM:264470; 2020.07.27]
The protein encoded by ACOX1, peroxisomal acyl-CoA oxidase, is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. [Gene Cards, ACOX1; 2020.07.27]
Peroxisomal beta-oxidation of fatty acids is catalyzed by enzymes that are immunologically distinct from the analogous mitochondrial enzymes. The ACOX1 gene encodes peroxisomal acyl-CoA oxidase, the first and rate-limiting enzyme in the peroxisomal fatty acid beta-oxidation pathway. [from MIM:609751; 2020.07.27]
Many to many: multiple related genes in both species.
High-scoring ortholog of human ACOX1; additional related genes in both species. Dmel\ ACOX1 shares 44% identity and 63% similarity with human ACOX1.
